Dose-Dependent Effects of Caffeine Citrate in Preterm Infants: A Retrospective Analysis of Weight Gain and Cardiac Outcomes

Abstract

Objective: A xanthine, caffeine citrate (CC), increases the metabolic rate with the release of catecholamine and affects weight gain in these patients in the first days. The cardiovascular system increases cardiac output and average arterial blood pressure by increasing heart rate, cardiac contractility, and stroke volume. This study investigated the effects of 5 and 10 mg/kg/day doses of CC on early postnatal weight gain velocity, discharge weight percentile, and cardiac function parameters in preterm infants.

Methods: Neonates who underwent CC-therapy between January 2020 and April 2023 and were ≤34 weeks gestation were included in this retrospective analysis. Twenty-three patients were given 5 mg/kg maintenance CC (group 1). Twenty-three patients were given 10 mg/kg maintenance CC (group 2). The groups were compared in terms of demographic data, complications of prematurity (RDS, BPD, NEC, IVH, ROP, PDA), type and duration of respiratory support, time to birth weight, time to total enteral nutrition, discharge weight percentile, and echocardiography (Echo) findings. Data for groups 1 and 2 were examined independently.

Results: The study included 46 neonates. Patients in group-1 (11± 6.1 day) achieved their birth weight for a statistically significant shorter period compared to group-2 (15± 5 day) (p <.05). The groups did not differ in any way regarding time to transition to full enteral nutrition, discharge weight percentile, discharge time, echocardiographic results, premature complication, type and duration of respiratory support.

Conclusion: Babies receiving CC at a dose of 5 mg/kg/day achieved their birth weight in a shorter time than those receiving 10 mg/kg/day. Both dosage regimens have similar safety in terms of side effects, weight gain after the first week, and cardiological aspects.

Keywords

• Caffeine citrate
• neonates
• gain weight
• cardiologic side effects
• neonatal nutrition

References

1. Montenegro BL, Amberson M, Veit L, Freiberger C, Dukhovny D, Rhein LM. Economics of home monitoring for apnea in late preterm infants. Respiratory care. 2017;62(1):42-48. google scholar
2. Rostas SE, McPherson C. Caffeine Therapy in Preterm Infants: The Dose (and Timing) Make the Medicine. Neonatal Network. 2019;38(6) google scholar
3. Long J-Y, Guo H-L, He X, Hu Y-H, Xia Y, Cheng R et al. Caffeine for the pharmacological treatment of apnea of prematurity in the NICU: dose selection conundrum, therapeutic drug monitoring and genetic factors. Frontiers in Pharmacology. 2021;12:681842. google scholar
4. Huvanandana J, Thamrin C, McEwan AL, Hinder M, Tracy MB. Cardiovascular impact of intravenous caffeine in preterm infants. Acta Paediatrica. 2019;108(3):423-429. google scholar
5. Philip RK, Ismail A, Murphy B, Mirza A, Quinn C, Dunworth M. Caffeine treatment for apnea of prematurity and the influence on dose-dependent postnatal weight gain observed over 15 years. Journal of Caffeine and Adenosine Research. 2018;8(3):99-106. google scholar
6. Lopez L, Saurers DL, Barker PC, Cohen MS, Colan SD, Dwyer J et al. Guidelines for performing a comprehensive pediatric transthoracic echocardiogram: recommendations from the American Society of Echocardiography. Journal of the American Society of Echocardiography. 2024;37(2):119-170. google scholar
7. Hussain I, Kumar M, Ali A, Naz F, Khan WA, Salat MS et al. Dose–Response Study of Caffeine on Postnatal Weight Gain in Premature Neonates—A Retrospective Cohort Study. Dose-Response. 2024;22(2):15593258241247185. google scholar
8. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlssonet A et al. Long-term effects of caffeine therapy for apnea of prematurity. New England Journal of Medicine. 2007;357(19):1893-1902. google scholar

9. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlssonet A et al. Caffeine therapy for apnea of prematurity. New England Journal of Medicine. 2006;354(20):2112-2121. google scholar
10. Faramarzi F, Shiran M, Rafati M, Farhadi R, Salehifar E, Nakhshab M. The efficacy and safety of two different doses of caffeine on the respiratory function of preterm infants. Caspian Journal of Internal Medicine. 2018;9(1):46. google scholar
11. Mohammed S, Nour I, Shabaan AE, Shouman B, Abdel-Hady H, Nasef N. High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial. European journal of pediatrics. 2015;174:949-956. google scholar
12. Vliegenthart R, Miedema M, Hutten GJ, van Kaam AH, Onland W. High versus standard dose caffeine for apnoea: a systematic review. Archives of disease in childhood-fetal and neonatal edition. 2018;103(6):F523-F529. google scholar
13. Pakvasa MA, Saroha V, Patel RM. Optimizing caffeine use and risk of bronchopulmonary dysplasia in preterm infants: a systematic review, meta-analysis, and application of grading of recommendations assessment, development, and evaluation methodology. Clinics in Perinatology. 2018;45(2):273-291. google scholar
14. Chen J, Jin L, Chen X. Efficacy and safety of different maintenance doses of caffeine citrate for treatment of apnea in premature infants: a systematic review and meta‐analysis. BioMed Research International. 2018;2018(1):9061234. google scholar
15. Brattström P, Russo C, Ley D, Bruschettini M. High‐versus low‐dose caffeine in preterm infants: a systematic review and meta‐analysis. Acta Paediatrica. 2019;108(3):401-410. google scholar
16. Lista G, Fabbri L, Polackova R, Kiechl-Kohlendorfer U, Papagaroufalis K, Saenz P et al. The real-world routine use of caffeine citrate in preterm infants: a European postauthorization safety study. Neonatology. 2016;109(3):221-227. google scholar
17. Romagnoli C, De Carolis MP, Muzii U, Zecca E, Tortorolo G, Chiarotti M et al. Effectiveness and side effects of two different doses of caffeine in preventing apnea in premature infants. Therapeutic drug monitoring. 1992;14(1):14-19. google scholar
18. Parladori R, Austin T, Smielewski P, Czosnyka M, Paoletti V, Vitali F et al. Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period. Pediatric Research. 2024;96(5):1267-1274. google scholar
19. Walther FJ, Erickson R, Sims ME. Cardiovascular effects of caffeine therapy in preterm infants. American Journal of Diseases of Children. 1990;144(10):1164-1166. google scholar